Vesicare, pills 10mg, 30pcs

Composition

Each 10 mg tablet contains:

composition of the tablet core:  solifenacin succinate 10.0 mg, lactose monohydrate 102.5 mg, corn starch 30.0 mg, hypromellose 3 MPas-6.0 mg, magnesium stearate-1.5 mg, purified water* – 54.0 mg;

composition of the film coating of the tablet:  opadray pink 03F14895 – 4.0 mg (hypromellose 6 MPa s-62.0%, talc-18.59%, macrogol 8000-11.63%, titanium dioxide-7.75%, iron oxide red-0.03%), purified water* – 36.0 mg

. * – water is removed during production.

Pharmacological action

Mechanism of action Solifenacin is a specific competitive antagonist of muscarinic receptors. The bladder is innervated by parasympathetic cholinergic nerves. Acetylcholine acts on muscarinic receptors (mainly M3) and causes detrusor contraction Pharmacological studies conducted in vitro and in vivo have shown that solifenacin is a specific competitive inhibitor of muscarinic receptors of the M 3 subtype. It has also been found that solifenacin has low or no affinity for various other receptors and ion channels. Pharmacodynamics The efficacy of Vesicar in doses of 5 mg and 10 mg, studied in several double-blind, randomized, controlled clinical trials in men and women with overactive bladder syndrome, was observed during the first week of treatment and stabilized over the next 12 weeks of treatment. A long-term open-label clinical trial showed that the effectiveness is maintained for at least 12 months. After 12 weeks of use, approximately 50% of patients who suffered from urinary incontinence before treatment stopped experiencing urinary incontinence, and 35% of patients achieved a reduction in the frequency of urination to less than 8 per day. Treatment of symptoms of overactive bladder (OAB) resulted in significant improvements in quality of life. The maximum effect of Vesicar can be detected after 4 weeks. Pharmacokinetics General Characteristicsabsorption: Maximum plasma concentration (Cmax) is reached after 3-8 hours. The time to reach the maximum concentration (tmax) does not depend on the dose. Cmax and area under the curve (AUC) of concentration versus time increase in proportion to the dose increase from 5 to 40 mg. Absolute bioavailability is 90%. Food intake does not affect the Cmax and AUC of solifenacin. Distribution: The volume of distribution of solifenacin after intravenous use is approximately 600 liters. Solifenacin is largely (about 98%) bound to plasma proteins, mainly to α1-acid glycoprotein. Metabolism: Solifenacin is extensively metabolized by the liver, mainly by the CYP3A4 isoenzyme. However, there are alternative metabolic pathways through which solifenacin can be metabolized. The systemic clearance of solifenacin is about 9.5 l / h, and the final half-life is 45-68 hours. After oral use, the following metabolites were identified in plasma in addition to solifenacin: one pharmacologically active (4R-hydroxysolifenacin) and three inactive (N-glucuronide, N-oxide and 4R-hydroxy-N-oxide of solifenacin). Elimination: After a single use of 10 mg of 14C-labeled solifenacin after 26 days, about 70% of radioactivity was detected in the urine and 23% in the faeces. In the urine, approximately 11% of radioactivity was detected as an unchanged Active ingredient, about 18% as an N-oxide metabolite,9% as a 4R-hydroxy-N-oxide metabolite, and 8% as a 4R-hydroxy metabolite (active metabolite). The pharmacokinetics of solifenacin are linear in the therapeutic dose range. Features of pharmacokinetics in certain categories of patientscast: There is no need to adjust the dose depending on the age of patients. Studies have shown that solifenacin exposure (5 and 10 mg), expressed as AUC, was similar in healthy elderly individuals (65 to 80 years) and in healthy young individuals (The mean absorption rate, expressed as tmax, was slightly lower, and the terminal half-life was approximately 20% longer in older adults. These minor differences are not clinically significant. The pharmacokinetics of solifenacin have not been determined in children and adolescents. Gender: The pharmacokinetics of solifenacin are independent of the patient’s gender. Race: Race does not affect the pharmacokinetics of solifenacin. Renal insufficiency: The AUC and Cmax of solifenacin in patients with mild to moderate renal insufficiency differ slightly from the corresponding values in healthy volunteers. In patients with severe renal insufficiency (creatinine clearance There was a statistically significant relationship between creatinine clearance and solifenacin clearance. Pharmacokinetics in patients undergoing hemodialysis have not been studied. Hepatic insufficiency: In patients with moderate hepatic insufficiency (Child-Pugh stage B), the Cmax value does not change, AUC increases by 60%, and t1 / 2 doubles. Pharmacokinetics in patients with severe hepatic insufficiency were not determined.

Indications

Treatment of urgent (imperative) urinary incontinence, frequent urination, and urgent (imperative) urge to urinate characteristic of patients with overactive bladder syndrome.

Use during pregnancy and lactation

There are no clinical data on women who became pregnant while taking solifenacin. Animal studies have shown no direct adverse effects on fertility, embryo/fetus development, or delivery.

Caution should be exercised when prescribing this drug to pregnant women only if the potential benefit to the mother outweighs the potential risk to the fetus.

There are no data on the excretion of solifenacin in breast milk. In mice, solifenacin and / or its metabolites were excreted in breast milk and caused a dose-dependent developmental disorder in newborn mice. The use of Vesicar is not recommended during breastfeeding.

Contraindications

• Urinary retention.
• severe gastrointestinal diseases (including toxic megacolon).
• myasthenia gravis.
• angle-closure glaucoma.
• hypersensitivity to the Active ingredient or any of the excipients.
• performing hemodialysis.
• severe liver failure.
• severe renal insufficiency or moderate hepatic insufficiency with concomitant treatment with strong inhibitors of the CYP3A4 isoenzyme, such as ketoconazole (see the section “Interaction with other drugs”).
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
• children under 18 years of age.

With caution

Before starting treatment with Vesicar, it should be established whether there are no other causes of urination disorders (heart failure or kidney disease). If a urinary tract infection is detected, appropriate antibacterial treatment should be initiated. Vesicar should be administered with caution to patients:

• with clinically significant obstruction of the bladder outlet leading to the risk of urinary retention.
• with gastrointestinal diseases with obstruction.
• with the risk of reduced gastrointestinal motility.
• patients with severe renal insufficiency (creatinine clearance <30 ml / min) and moderate hepatic insufficiency (Child-Pugh stage B); doses for these patients should not exceed 5 mg
• . concomitantly taking a strong inhibitor of the CYP3A4 isoenzyme, for example, ketoconazole. patients with hiatal hernia, gastroesophageal reflux, and patients taking concomitant medications (such as bisphosphonates) that may cause or worsen esophagitis.
• with autonomic neuropathy.

Side effects

Most often – dryness of the oral mucosa (11% – when taken at a dose of 5 mg per day,22% – 10 mg per day). Frequent (more than 1/100 and less than 1/10), infrequent (more than 1/1,000 and less than 1/100), rare (more than 1/10000 and less than 1/1000).

From the digestive system: frequent-constipation, nausea, dyspepsia, abdominal pain; infrequent-gastroesophageal reflux disease, dry pharyngeal mucosa; rare-intestinal obstruction, coprostasis.

From the nervous system: infrequent-drowsiness, taste disorders.

From the sensory organs: frequent-blurred visual perception (violation of accommodation); infrequent-dryness of the eye mucosa.

From the respiratory system: infrequent-dryness of the nasal mucosa.

Skin disorders: infrequent – dry skin.

From the urinary system: infrequent – difficult urination; rare-delayed urination.

Other: infrequent – urinary tract infections, fatigue, peripheral edema.

Interaction

Pharmacological interaction

Concomitant treatment with drugs with anticholinergic properties may lead to more pronounced therapeutic and undesirable effects. After stopping taking solifenacin, you should take a break of approximately one week before starting treatment with another anticholinergic drug.

The therapeutic effect may be reduced by concomitant use of cholinergic receptor agonists. Solifenacin may reduce the effect of medications that stimulate gastrointestinal motility, such as metoclopramide and cisapride.

Pharmacokinetic interaction

In vitro studies have shown that at therapeutic concentrations, solifenacin does not inhibit CYP1A1/2,2C9,2C19,2D6 or ZA4 isoenzymes isolated from human liver microsomes. Therefore, it is unlikely that solifenacin will alter the clearance of drugs metabolized by these CYP enzymes.

Effects of other drugs on the pharmacokinetics of solifenacin

Solifenacin is metabolized by the CYP3A4 isoenzyme. Concomitant use of ketoconazole (200 mg / day), a strong inhibitor of the CYP3A4 isoenzyme, caused a twofold increase in the AUC of solifenacin concentration versus time, and a three – fold increase at a dose of 400 mg/day.

Therefore, the maximum dose of Vesicar should not exceed 5 mg if the patient is simultaneously taking ketoconazole or therapeutic doses of other strong inhibitors of the CYP3A4 isoenzyme (such as ritonavir, nelfinavir, itraconazole). Concomitant treatment with solifenacin and a strong inhibitor of the CYP3A4 isoenzyme is contraindicated in patients with severe renal insufficiency or moderate hepatic insufficiency. The effects of enzyme induction on the pharmacokinetics of solifenacin and its metabolites, as well as the effect of high-affinity substrates of the CYP3A4 isoenzyme on the action of solifenacin, have not been studied.

Since solifenacin is metabolized by the CYP3A4 isoenzyme, pharmacokinetic interactions with other substrates of the CYP3A4 isoenzyme with higher affinity (verapamil, diltiazem) and with inducers of the CYP3A4 isoenzyme (rifampicin, fenitoin, carbamazepine) are possible.

Effect of solifenacin on the pharmacokinetics of other drugs Oral contraceptives: There was no pharmacokinetic interaction between solifenacin and combined oral contraceptives (ethinyl estradiol / levonorgestrel). Warfarin: Vesicar use did not cause changes in the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.

Digoxin: Taking Vesicar did not affect the pharmacokinetics of digoxin.

How to take, course of use and dosage

Adults, including the elderly

5 mg once a day inside, whole, washed down with liquid, regardless of the time of meal. If necessary, the dose can be increased to 10 mg once a day.

The safety and efficacy of Vesicar in children has not been studied. Therefore, do not use Vesicar in children.

Patients with renal insufficiency No dose adjustment is required in patients with mild or moderate renal insufficiency (creatinine clearance > 30 ml / min). Patients with severe renal insufficiency (creatinine clearance

Patients with hepatic insufficiency No dose adjustment is required in patients with mild hepatic insufficiency. In patients with moderate hepatic insufficiency (Child-Pugh stage B), solifenacin should be administered with caution and should not be administered more than 5 mg per day.

Patients receiving strong CYP3A4 inhibitors The maximum dose of Vesicar should be limited to 5 mg when taken in combination with ketoconazole or the therapeutic dose of another CYP3A4 inhibitor (ritonavir, nelfinavir, itraconazole).

Overdose

The highest dose of solifenacin used by the volunteers was 100 mg as a single dose. The most common side effects reported at this dose were headache (mild), dry mouth (moderate), dizziness (moderate), drowsiness (mild), and blurred vision (moderate). No cases of acute overdose have been reported. In cases of overdose, you should prescribe activated charcoal, do gastric lavage, but do not induce vomiting.

As with overdoses of other anticholinergic agents, symptoms should be treated as follows::* for severe central anticholinergic effects (hallucinations, severe excitability) – physostigmine or carbachol; * for convulsions or severe excitability – benzodiazepines;• in case of respiratory failure – artificial respiration;• for tachycardia-beta blockers; * if urination is delayed – catheterization; * for mydriasis – instill pilocarpine in the eyes and / or place the patient in a dark room.

As in the case of overdose of other anticholinergic drugs, special attention should be paid to patients with an established risk of prolongation of the QT interval (i. e., with hypokalemia, bradycardia and concomitant use of drugs that cause prolongation of the QT interval) and patients with heart diseases (myocardial ischemia, arrhythmias, congestive heart failure).

Special instructions

Before starting treatment with Vesicar, you should determine whether there are other causes of frequent urination (heart failure or kidney disease). If a urinary tract infection is detected, appropriate antibacterial treatment should be initiated. Vesicar should be administered with caution to patients:* with clinically significant obstruction of the bladder outlet leading to the risk of urinary retention;• patients with gastrointestinal obstructive diseases;• with the risk of reduced gastrointestinal motility;• patients with severe renal (creatinine clearance) • concomitantly taking a strong CYP3A4 inhibitor, such as ketoconazole • * with hiatal hernia, gastroesophageal reflux, and patients taking concomitant medications (such as bisphosphonates) that may cause or exacerbate esophagitis;• with autonomic neuropathy.

Patients with rare hereditary problems of galactose tolerance, lapidary (Sami) lactase deficiency, glucose-galactose malabsorption should not take the drug.

Influence on the ability to drive a car and operate mechanisms

Solifenacin, like other anticholinergic drugs, can cause blurred vision, as well as (rarely) drowsiness and fatigue, which can negatively affect the ability to drive a car and work with mechanisms.

Form of production

Coated tablets.

Active ingredient

Solifenacin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as prescribed by a doctor, for pregnant women as prescribed by a doctor

Indications

Enuresis